GENERAL METHODS FOR SYNTHESIS OF BIOACTIVE HETEROCYCLES

本申请中描述的研究的长期目标是 开发新的立体控制方法来合成各种 不饱和杂环体系。绝大多数的制药公司使用 在医学实践中是杂环化合物。我们相信，通过开发高效的 合成进入杂环系统，我们将允许有希望的 药学引领未来快速发展，潜力巨大 治疗方面的影响。 杂环化反应是我们建议的研究的重点 04至07项目年。这种类型的自行车运动效果要差得多。 开发了比相应的碳环多烯制备方法 骑自行车运动。我们的注意力将继续集中在杂环化反应上 以乙烯基硅烷为端基。自从我们推出了这些 在1980年的环化终止剂中，乙烯基硅烷已被证明在 终止各种环化反应的实验室数量 反应。因为新发起人计划在其中扮演关键角色 拓展杂环化化学的视野，我们的目标也是 开发新的氮杂环和草环环化引发剂。 四氢吡啶类药物与帕金森病刺激物MPTP， 都会做好准备。新的抗生素链他唑林将于#年制备 对映体选择性形式，以及强大的“子宫疏散”二萜 佐拉帕诺。 中间体和天然产品目标将广泛扩大到 壳牌生物科学研究中心的生物活动 开发公司，以及在NCI。

The long-term objective of the research described in this application is to develop new stereocontrolled methods for the synthesis of a variety of unsaturated heterocyclic systems. The vast majority of pharaceuticals used in medical practice are heterocycles. We believe by developing efficient synthetic entries to heterocyclic ring systems, we will allow promising pharacological leads in the future to be rapidly developed with potential therapeutic implications. Heterocyclization reactions are the focus of the studies we propose for the 04 to 07 project years. Cyclizations of this type are much less well developed than the corresponding preparation of carbocycles by polyene cyclizations. Our attention will continue to focus on heterocyclizations which are terminated by vinylsilanes. Since our introduction of these cyclization terminators in 1980, vinylsilanes have proven useful in a number of laboratories to terminate a wide variety of cyclization reactions. Because of the pivotal role that new initiators plan in expanding the horizons of heterocyclization chemistry, we also aim to develop new azacyclic and oxacyclic cyclization initiators. Tetrahydropridines related to the Parkinson's disease stimulaten, MPTP, will be prepared. The new antibiotic streptazolin will be prepared in enantioselective form, as will the powerful "uteroevacuant" diterpene zoapatanol. Intermediates and natural product targets will be broadly sdcrened for biological activity at the Biological Sciences Research Center of the Shell Development Co., and at NCI.